for people ages 4 months to 36 months (full criteria)
at Oakland, California and other locations
study started
estimated completion



PBGM01 is a gene therapy for GM1 gangliosidosis intended to deliver a functional copy of the GLB1 gene to the brain and peripheral tissues. This study will assess in a 2-stage design the safety, tolerability and efficacy of this treatment in patients with early onset infantile (Type 1) and late onset infantile (Type 2a) GM1 gangliosidosis. Results from the Type 1 and Type 2a groups will be assessed separately.

Official Title

Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Tolerability and Efficacy of a Single Dose of PBGM01 Delivered Into the Cisterna Magna of Subjects With Type 1 (Early Onset) and Type 2a (Late Onset) Infantile GM1 Gangliosidosis


PBGM01 is an adeno-associated viral vector serotype Hu68 carrying GLB1, the gene encoding for human beta-galactosidase, formulated as a solution for injection into the cisterna magna. This is a global interventional, multicenter, single-arm, dose escalation, adaptive design study of PBGM01 delivered as a one-time dose administered into the cisterna magna to patients with infantile GM1 gangliosidosis. There are two infantile subtypes of GM1 gangliosidosis: early onset infantile (Type 1) and late onset infantile (Type 2a) which are defined by the age of onset of disease symptoms. Early Onset Infantile (Type 1): - Onset <6 months of age - Age at enrollment: >4 to <24 months of age Late Onset Infantile (Type 2a): - Onset >6 to 18 months of age - Age at enrollment: >6 to <36 months of age (except Cohort 1 will be >12 to <36 months of age) In Part 1 of the study, two dose levels of PBGM01 will be studied separately in patients with either Type 1 or Type 2a GM1 gangliosidosis (see table below). The cohorts for patients with Type 1 and Type 2a will be assessed independently from each other. Part 1 will enroll a total of four cohorts, enrolled sequentially with separate dose-escalation cohorts for Type 1 GM1 and Type 2a GM1. Enrollment will initiate in Cohort 1. Following completion of Cohort 1, simultaneous enrollment in Cohort 2 and Cohort 3 will occur. Cohort 4 will follow completion of cohort 3. Part 2 of the study will test the safety and efficacy of PBGM01 in confirmatory cohorts for Types 1 and Type 2a GM1 gangliosidosis with a dose chosen based on the data obtained in part 1 of the study. This will be a 2-year study with a 3-year safety extension.


GM1 Gangliosidosis, GM1 Gangliosidosis, Type I, GM1 Gangliosidosis, Type 2, Beta-Galactosidase-1 (GLB1) Deficiency, Infantile, Late Infantile, Rare disease, Lysosomal storage disease, Gangliosidoses, Gangliosidosis, GM1, PBGM01


You can join if…

Open to people ages 4 months to 36 months

  • All Patients: Documented GM1 gangliosidosis diagnosis based on genotyping confirming 2 mutations in the GLB1 gene and documented deficiency of beta-galactosidase enzyme by laboratory testing
  • Age: 4 to 36 months (first cohort will be 12-36 months)


  • Early onset infantile (Type 1): Subjects who have signs and/or symptoms of GM1 gangliosidosis that started at or before 6 months of age and have specific developmental milestones remaining
  • Late onset infantile (Type 2a): Subjects who have signs and/or symptoms of GM1 gangliosidosis that started between 6 and 18 months of age and have specific developmental milestones remaining

You CAN'T join if...

  1. Any clinically significant neurocognitive deficit not attributable to GM1 gangliosidosis or any other condition that may, in the opinion of the investigator, confound interpretation of study results.
  2. If a subject had an acute illness requiring hospitalization within 30 days of enrollment, the history must be discussed with the sponsor's medical monitor before allowing the subject to be enrolled.
  3. History of ventilation assisted respiratory support or a need for tracheostomy as a result of their disease.
  4. Intractable seizure or uncontrolled epilepsy defined as having had an episode of status epilepticus, or seizures requiring hospitalization within 30 days prior to dosing of PBGM01.
  5. Any contraindication to the ICM administration procedure, including contraindications to fluoroscopic imaging and anesthesia or any condition that would increase the risk of adverse outcomes from the ICM procedure including, but not limited to, the presence of a space occupying lesion causing mass effects or signs of increased intracranial pressure, space occupying lesion in the posterior fossa or foramen magnum, aberrant vascular anatomy such as a large midline posterior inferior cerebellar artery, aberrant venous anatomy such as a large cerebellar vein or occipital sinus, or congenital anatomical abnormalities such as a Chiari malformation.
  6. Any contraindication to MRI or lumbar puncture (LP).
  7. Prior gene therapy.
  8. Use of miglustat within 48 hours prior to dosing of PBGM01. The use of miglustat is prohibited throughout the study.
  9. Use of enzyme replacement therapy or other investigational therapy within 5 half-lives prior to dosing of PBGM01. The use of enzyme replacement is prohibited throughout the study.
  10. . Receipt of a vaccine within 14 days of dosing.
  11. . Estimate glomerular filtration rate (eGFR) <30 mL/minute based on creatinine
  12. . Coagulopathy (INR > 1.5) or activated partial thromboplastin time [aPTT] > 40 seconds
  13. . Thrombocytopenia (platelet count < 100,000 per μL.
  14. . AST or ALT > 3 times the upper limit of normal (ULN) or total bilirubin > 1.5x ULN
  15. . Cardiomyopathy (screening troponin level above the ULN).
  16. . Peripheral neuropathy
  17. . Medical conditions or laboratory or vital sign abnormalities that would increase risk of complications from intra-cisterna magna injection, anesthesia, fluoroscopy, LP, and/or MRI including temperature over 38°C, oxygen saturation below 95% on room air or baseline oxygen requirement, heart rate or respiratory rate abnormal for age of the subject, abnormal blood pressure for age, or evidence of infection.
  18. . Any condition (e.g., history of any disease, evidence of any current disease, any finding upon physical examination, or any laboratory abnormality) that, in the opinion of the investigator, would put the subject at undue risk during the administration procedure or would interfere with evaluation of PBGM01 or interpretation of subject safety or study results.


  • Benioff Children's Hospital accepting new patients
    Oakland California 94158 United States
  • University of Minnesota accepting new patients
    Minneapolis Minnesota 55455 United States


accepting new patients
Start Date
Completion Date
Passage Bio, Inc.
Phase 1/2 research study
Study Type
Expecting 20 study participants
Last Updated